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Reduction of blood pressure and albuminuria in hypertensive patients with type 2 diabetes using candesartan, lisinopril and their combination
$86
Poster Session 1
Night/day BP ratios and percent nighttime BP fall also. Subjects with a nocturnal fall in either sBP or dBP of less than 10% of daytime values were classified as non-dippers. Results: Both sBP (111 4- 7.1 vs. 104 49mmHg; p = 0.003) and dBP nighttime (66 4- 6.1 vs. 61 4- 5.3mmHg; p = 0.001) were higher in diabetic patients than non-diabetic subjects. Night/day ratios for sBP (0.93 4- 0.04 vs. 0.89 4- 0.05; p = 0.006) and dBP (0.86 4- 0.06 vs. 0.82 + 0.06; p = 0.007) were higher in diabetics. The loss of a fall in sBP was more prevalent in diabetic subjects (78 vs. 39%; p = 0.007). Non-dippers for sBP and dBP in the diabetic group had higher BP burden during the nighttime (21.4 4- 16.6 vs. 3.2 4- 3.9%; p = 0.01 and 21.9 4- 10 vs. 3.7 4- 5.5%; p < 0.001, respectively). Condnsions: Our data demonstrate higher sBP and dBP during the nighttime and loss of the nocturnal fall in BP in type 1 diabetic patients. Further prospective studies are needed to define if high BP burden in diabetic non-dippers during the night could represent a risk for nephropathy and cardiovascular disease.
P383 Hypertension in Type 2 Diabetics and the Associated Risk Factors (A Tip oftbe Iceburg!) M.G. UVARAJ. Speciality & Research centre, Salem, TN, India Aim: To know the extent of existence of newlydetected Diabetic hypertensives and already existing Diabetic hypertensives from our diabetic clinic and the common practical risk factors associated with them, are analysed. Strategy: Among the 500 Type 2 diabetic patients, 172(34.4%) Total diabetic hypertensives are detected. Age ranges 30 to 80 yrs. Mean Systolic pressure was 153.7mm of Hg and mean diastolic pressure was 93.3mm of Hg. Among the 172 Total Diabetic Hypertensives, Following Datas are analysed: 1) Newly detected diabetic hypertensives are 105(61%), And Already exsisting DM, HT are 67(38.9%). Where Male is 102(59.3%), and Female is 70(40%), 2) 163(94.7%) Patients are Non vegetarian, where Male is 101(61.9%), Female is 62(38%). 3) 125(72.6%) are Sedentary, where Male is 75(60%), Female is 50(40%). 4) 44(25.5%) Patients are obese where Male is 26(59%), Female is 18(40.9%). 5) 40(23.25%) Patients are alcoholics, where Male is 39(97.5%), and Female is 1(2.5%). 6) 37(21.5%) Patients are smokers, where Male is 37(100%), Female is nil. Conclusion: The Prevalance of hypertension(34.4%) is very high in diabetic population (Generalpopulation 10-20%) The Increased no of Newly detected diabetic hypertensives shows the lack of awareness (Tip of the Iceburg). The Altered Diet habits, Irregular exercise, and the nature of work plays a major roll with the Diabetic hypertensives, needs a lot of awareness and further study in India.
P384 Evaluation of Antihypertensive Treatment in Type 2 Diabetes M. BOZ 1,2, G. Michel 2. / Department oflnternal Medicine, Diabetes Clinical Center of Dr B. Beler, V. Gureba, Hospital, lstanbul; 2 Department of Endocrinology and Diabetology, Centre Hospitalier de Luxembourg It is well known that hypertension in type 2 diabetic patients is difficult to control. Aim of the study: to evaluate the results of treatment for hypertension in 37 patients with type 2 diabetes (22 males and 15 females). We compared this group of diabetic patients treated for hypertension (group 1) with a group of type 2 diabetic patients who had no antihypertensive treatment (group 2). All patients had oral antidiabetic drugs. 64% of patients of the first group were treated with an ACE inhibitor. Clinical characteristics of these patients were: (mean 4- SD): age (years):
62 4- 11 (range: 40-84), diabetes duration: 10.51 4- 6.81 years (range: 1-33), weight (kg): 84.67 4- 16 (range: 62-134), height (cm): 168.61 49.23 (range: 162-190), BMI (Body Mass Index: kg/m2): 29.67 4- 4.28 (range: 22.39-43.76), circumference of waist (cm): 104.63 4- 13.54 (range: 84-122), circumference of hip (cm): 109.72 + 12.34 (93-144), waist/hip ratio: 0.95 4- 0.07 (range: 0.8-1.1), systolic blood pressure (sBP mm Hg): 156.53 4- 18.43 (range: 120-190), diastolic blood pressure (dBP mm Hg): 89.17 4- 11.74 (range: 70-120), fasting glycemia (mg/dl): 201.8 452.93 (range: 105-320), C-peptide (ng/dl): 3.95 4- 4.51 (range: 0.61-23), creatinine (mg/dl): 0.99 4- 0.22 (range: 0.7-1.5), total cholesterol (mg/dl): 233.7 4- 45.39 (range: 160-330), triglyceridemia (mg/dl): 197.71 4- 121.52 (range: 44-478), HDL-cholesterol (mg/dl): 46 4- 17.98 (25-I00), HbAlc (%): 8.02 4- 1.92 % (range: 4.9-14.1), fasting insulinemia: 11.01 4- 4.52 mU/l (3.4-18.7), microalbuminuria: 77.16 4- 169.94/xg/ml/24 h (range: 8.5-278), familial history of hypertension: 21%, smoking: 24%, regular alcohol intake: 38%, coronary heart disease (ischemia and history of myocardial infarction): 17%, retinopathy (back-ground and proliferative): 24%. Results: sBP and dBP in the treated group are higher than in the group 2 (160.31 4- 19.36 vs. 153.5 4- 17.55 and 91.5 4- 14.8 vs. 87.25 -48.5 respectively, p < 0.1 for two comparisons). However the first group of patients are older (65.76 4- 9.37 vs. 58.4 4- 11.35 respectively, p < 0.02) and more obese (BMI: 30.55 4- 4.84 vs. 28.92 respectively, p < 0.1). The same group of patients shows markedly insulin resistance (12.37 4- 4.64 vs. 9.64 4- 4.15 respectively, p < 0.06), higher creatinine level (n.s) and microalbuminuria (134.58 4- 240 4- 98 vs. 27.93 4- 27.3 respectively, p < 0.08) than the second group of patients. Otherwise glycemic and lipidic parameters are not significantly different, but in group 1 are more patients with retinopathy (21% vs. 0% respectively, p < 0.04). In conclusion, treatment for hypertension in type 2 diabetes shows poor results on blood pressure due either to insulin resistance and/or patient compliance.
P385 Reduction of Blood Pressure and Albuminuria in Hypertensive Patients with Type 2 Diabetes Using Candesartan, Lisinopril and Their Combination CARL ERIK MOGENSEN, Mark E. Cooper. Medical Department. M, Aarhus University Hospital, Aarhus, Denmark; Department of Medicine, University Hospital Melbourne, Melbourne, Victoria, Australia Objectives: To study the effect of candesartan cilexetil (C) 16 mg o.d. and lisinopril (L) 20 mg o.d. and their combination (C+L) on blood pressure (BP) and urinary albumin excretion in hypertensive type 2 diabetic patients with microalbuminuria. Design and Methods: Patients (n= 199), aged 30-75 years with sitting diastolic blood pressure (DBP) 90-110 mmHg and urinary albumin/creatinine ratio (UACR) of 2.5-25 mg/mmol were, after 4 weeks of placebo treatment, randomised double blind to receive either, C or L monotherapy for 12 weeks followed by an additional 12 weeks of the same monotherapy or the combination of C+L. Results: After 12 weeks of monotherapy, both C and L reduced sitting BP (C 12.4/9.5 mmHg p<0.001; L 15.7/9.7 mmHg p<0.001) and UACR (C 30% p<0.001; L 46% p<0.001) with no significant difference between treatments. After the 24 week treatment period, UACR decreased in all treatment groups (C 24% p---0.052; L 39% p<0.001; C+L 50% p<0.001). At 24 weeks, the C +L treatment group had a BP reduction of 25.3/16.3 mmHg (p<0.001) as compared to baseline. This reduction was substantially and significantly greater than the reductions observed with monotherapy (C 14.1/10.4 p<0.001; L 16.7/10.7 p<0.001). Both drugs and their combination were well tolerated and there were no major differences in adverse event profiles. Importantly, no adverse effects were observed in the combination treatment group such as acute deterioration in renal function or symptomatic hypotension. Conclusion: ATt receptor blockade with candesartan and ACE inhibition with lisinopril both reduce BP and microalbuminuria (UACR) in hypertensive type 2 diabetic patients with microalbuminuria with no significant
Track 2. Clinical Research & Care difference between the treatments. The combination of candesartan and lisinopril reduced BP more than any of the monotherapies and appeared to be the most effective treatment in reducing UACR. Thus the combination of candesartan, and lisinopril, seems a highly effective and well tolerated treatment for reducing BP in hypertensive type 2 diabetic patients with microalbuminuria.
P386 12 Months Post UKPDS and HOT: Impact on BP Targets and Anfihypertensive Drug Prescribing in the Community M.N. MUNRO, R. Larenson, M.D. Feher. Beta Cell Diabetes Centre, Chelsea & Westminster Hospital, London, UK The influence of UKPDS and HOT trials results on community-based prescriptions of antihypertensive drugs in order to achieve lower BP targets for the observed clinical benefit has not been reported. From a single Primary Care Group in Southern England (population 42,000) patients with confirmed type 2 diabetes (n=415) were characterised by current BP recordings and number and class of antihypertensive drug used. From this group, BPs above that achieved in the trials (above 140/80mmHg) were observed in only 40% of subjects, while antihypertensive drug usage was recorded in 54%, of whom 33% were on two or more antihypertensive drugs. When medication usage was stratified according to BP control, 64% of subjects with a systolic BP> 140mmHg were receiving antihypertensive medication and 59% in those with a diastolic BP>80mmHg. Treatment with 2 or more antihypertensives was recorded in 34% in both the higher BP groups. (In comparison, two thirds of UKPDS and HOT patients were similarly treated). Only 3% of patients were on >3 antihypertensive agents. Low usage was recorded for beta-blockers (10%), alpha-blockers (4%) and A-II blockers (2%). Increased use was recorded for calcium channel blockers (18%), diuretics (20%) and ACEI (21%). These data show there has been implementation of evidence based practice in the community. "Newer" compared to "old" antihypertensive treatment appear to be widely used. The number of patients needing antihypertensive treatment will need to be almost doubled if trial-based BP targets are to be reached. In addition, the numbers taking 3 or more antihypertensive drugs will need to be increased nearly 10x if their management reflects UKPDS. The cost of implementing this in the short term is likely to be very substantial in Primary Care.
P387 New Drug Combinations in Diabetic Hypertension; Short Term Effects of Low Dose Moxonidine-ACEI Combination A. COX, A. Zambaninl, C. Mclntosfi, M.D. Feher. Beta Cell Diabetes Centre, Chelsea & Westminster Hospital, London, UK The recent major outcome trials In diabetic hypertension have highlighted the need for combination antihypertensive therapy in order to lower BP and reduce cardiovascular complications. There is little data on the role of moxonidine (a selective imidazoline receptor agonist) in combination antihypertensive treatment in patients with diabetes. In a cross-over study, eight subjects with type 2 diabetes and on conventional dose ACEI for hypertension (mean BP: 176/93, SD:26/6), were assessed three times: (1) after a 2 week run-in phase, with continuation of conventional dose ACEI (2) after 4 weeks low dose moxonidine (200mcg) combination with half usual dose ACEI treatment and (3) after 4 weeks treatment with only conventional dose ACEI. Standardised clinic BP measurements confirmed a mean reduction of 14/12mmHg (A dBP p<0.05 Wilcoxon) with low dose combination therapy and a 14/9mmHg increase (A sBP, dBP p<0.01) after moxonidine withdrawal and reintroduction of the usual dose ACEI. There were no significant changes in weight or fasting glucose or lipid profile. This study has shown the marked BP lowering effects of combining a low dose imldazoline agonist and ACEI, (as well as the effects of monotherapy
$87
withdrawal) and has the potential advantage of minimising drug related side-effects.
1'388 Idiotypic Antibodies in Autoimmunitary Diabetes Mellitus GUSTOVO ACOSTA 1, Maribel Hem~fndez2, Rocio Reyes 3, Martin Herrera4, Carlos Parrao 5, Rao Srinivasa6. J Immunology, Clinica de Inmunodiagntstico, M(xico, City, DE M(xico; 2 Immunology, Clinica de lnmunodiagn6stico, M(xico, City, DE M(xico; s Microbiology, Facultad de Medicina, UNAM, M~xico, City, DE M~xico; 4 Medicina lnterna, Hospital Jutrez de Mdxico, M(xico, City, DE Mdxico; 5 Laboratorio Clfnico, Hospital Judrez de Mtxico, Mdxico, City, DE M(xico; 6 Research and Development, Biomerica, CA, United States of America The regulation of the production of immunoglobulins by antibodies from the same person was postulated by Jerne when he demonstrated secuences of specific aminoacids in the antibodies of each person located in the variable portions of immunoglobulins which are genetically codified and can be antigenic and induce the production of new antibodies against these portions denominated idiotypes and regulate the production of autoantibodies to diminish the inflamatory effects in the pancreatic cells. In the current work the idiotypic induction to regulate the production of (IAA) in 6 patients with diabetes type 1, with a evolution time of 36 months that presents IAA peripheric blood quantified by ELISA and with a substitutive treatmen with human insulin. Individually the gamaglobulins of the 6 patients were purified by the Cohn method it consists of an initial precipitation with ethilic alcohol y then by cromatography affinity using human insulin fixed to Sepharosa 4B. Protocol of specific idiotypic antibodies induction: Daily administration of specific autologous autoantibodies via subcutaneous (0.5 ml) during 40 days. Protocol of inespecific idiotypic antibodies induction: autologous immunoglobulins were purified and administrated in a control group of 40 healthy persons with normal glucose levels and glycosilated hemoglobin at the begining of the study. At the end of the protocol circulanting antibodies weren't detected against human insulin (IAA) by the ELISA method in three patiens, diminishing significantly the dairy doses of insulin, and hemoglobin levels and glucose in fast remained in normal ranges at 60 days. In the control group there weren't variations in the concentration of glucose in fast and glycosilated hemoglobin during 40 days.
1'389 ~8-Cell Autoantibodies and Genetic Background Associated with Insulin Dependence in Adult-Onset Diabetes Mellitns SILVINA N. VALDEZ ~, Ana L. Villanueva l, Anabel Villalba 1, Ruben E Iacono 1, Mauricio P. Sica ', Alejandro C. Cardoso I, Maximiliano Wilda 2, C. Refi 3 Norberto Cedola 3, Gustavo Frechtel 2, Edgardo Poskus i. l Inmunologia, Facultad de Farmacia y Bioqu[mica, UBA e IDEHU (CONICET-UBA), Capital Federal, Buenos Aires, Argentina; 2 Gen(tica y Biolog[a Molecular, Facultad de Farmacia y Bioquimica, UBA, Capital Federal, Buenos Aires, Argentina; 3 Cenexa, Universidad Nacional de La PIata-CONICET, La Plata, Pcia de Buenos Aires, Argentina Immune-mediated Diabetes Mellitus (DM) is early detectable by determination of islet cell autoantibodies (markers). The most useful markers are the autoantibodies to insulin (IAA), antibodies to glutamic acid decarboxylase (GADA) and antibodies to protein tyrosine phosphatase (ICA512A). In this study we determined the presence of immunological and genetic markers in adult-onset diabetic patients. We studied 45 patients treated with insulin after two year from diagnosis ("fast-evolving insulin requiring
Poster Session 1
Night/day BP ratios and percent nighttime BP fall also. Subjects with a nocturnal fall in either sBP or dBP of less than 10% of daytime values were classified as non-dippers. Results: Both sBP (111 4- 7.1 vs. 104 49mmHg; p = 0.003) and dBP nighttime (66 4- 6.1 vs. 61 4- 5.3mmHg; p = 0.001) were higher in diabetic patients than non-diabetic subjects. Night/day ratios for sBP (0.93 4- 0.04 vs. 0.89 4- 0.05; p = 0.006) and dBP (0.86 4- 0.06 vs. 0.82 + 0.06; p = 0.007) were higher in diabetics. The loss of a fall in sBP was more prevalent in diabetic subjects (78 vs. 39%; p = 0.007). Non-dippers for sBP and dBP in the diabetic group had higher BP burden during the nighttime (21.4 4- 16.6 vs. 3.2 4- 3.9%; p = 0.01 and 21.9 4- 10 vs. 3.7 4- 5.5%; p < 0.001, respectively). Condnsions: Our data demonstrate higher sBP and dBP during the nighttime and loss of the nocturnal fall in BP in type 1 diabetic patients. Further prospective studies are needed to define if high BP burden in diabetic non-dippers during the night could represent a risk for nephropathy and cardiovascular disease.
P383 Hypertension in Type 2 Diabetics and the Associated Risk Factors (A Tip oftbe Iceburg!) M.G. UVARAJ. Speciality & Research centre, Salem, TN, India Aim: To know the extent of existence of newlydetected Diabetic hypertensives and already existing Diabetic hypertensives from our diabetic clinic and the common practical risk factors associated with them, are analysed. Strategy: Among the 500 Type 2 diabetic patients, 172(34.4%) Total diabetic hypertensives are detected. Age ranges 30 to 80 yrs. Mean Systolic pressure was 153.7mm of Hg and mean diastolic pressure was 93.3mm of Hg. Among the 172 Total Diabetic Hypertensives, Following Datas are analysed: 1) Newly detected diabetic hypertensives are 105(61%), And Already exsisting DM, HT are 67(38.9%). Where Male is 102(59.3%), and Female is 70(40%), 2) 163(94.7%) Patients are Non vegetarian, where Male is 101(61.9%), Female is 62(38%). 3) 125(72.6%) are Sedentary, where Male is 75(60%), Female is 50(40%). 4) 44(25.5%) Patients are obese where Male is 26(59%), Female is 18(40.9%). 5) 40(23.25%) Patients are alcoholics, where Male is 39(97.5%), and Female is 1(2.5%). 6) 37(21.5%) Patients are smokers, where Male is 37(100%), Female is nil. Conclusion: The Prevalance of hypertension(34.4%) is very high in diabetic population (Generalpopulation 10-20%) The Increased no of Newly detected diabetic hypertensives shows the lack of awareness (Tip of the Iceburg). The Altered Diet habits, Irregular exercise, and the nature of work plays a major roll with the Diabetic hypertensives, needs a lot of awareness and further study in India.
P384 Evaluation of Antihypertensive Treatment in Type 2 Diabetes M. BOZ 1,2, G. Michel 2. / Department oflnternal Medicine, Diabetes Clinical Center of Dr B. Beler, V. Gureba, Hospital, lstanbul; 2 Department of Endocrinology and Diabetology, Centre Hospitalier de Luxembourg It is well known that hypertension in type 2 diabetic patients is difficult to control. Aim of the study: to evaluate the results of treatment for hypertension in 37 patients with type 2 diabetes (22 males and 15 females). We compared this group of diabetic patients treated for hypertension (group 1) with a group of type 2 diabetic patients who had no antihypertensive treatment (group 2). All patients had oral antidiabetic drugs. 64% of patients of the first group were treated with an ACE inhibitor. Clinical characteristics of these patients were: (mean 4- SD): age (years):
62 4- 11 (range: 40-84), diabetes duration: 10.51 4- 6.81 years (range: 1-33), weight (kg): 84.67 4- 16 (range: 62-134), height (cm): 168.61 49.23 (range: 162-190), BMI (Body Mass Index: kg/m2): 29.67 4- 4.28 (range: 22.39-43.76), circumference of waist (cm): 104.63 4- 13.54 (range: 84-122), circumference of hip (cm): 109.72 + 12.34 (93-144), waist/hip ratio: 0.95 4- 0.07 (range: 0.8-1.1), systolic blood pressure (sBP mm Hg): 156.53 4- 18.43 (range: 120-190), diastolic blood pressure (dBP mm Hg): 89.17 4- 11.74 (range: 70-120), fasting glycemia (mg/dl): 201.8 452.93 (range: 105-320), C-peptide (ng/dl): 3.95 4- 4.51 (range: 0.61-23), creatinine (mg/dl): 0.99 4- 0.22 (range: 0.7-1.5), total cholesterol (mg/dl): 233.7 4- 45.39 (range: 160-330), triglyceridemia (mg/dl): 197.71 4- 121.52 (range: 44-478), HDL-cholesterol (mg/dl): 46 4- 17.98 (25-I00), HbAlc (%): 8.02 4- 1.92 % (range: 4.9-14.1), fasting insulinemia: 11.01 4- 4.52 mU/l (3.4-18.7), microalbuminuria: 77.16 4- 169.94/xg/ml/24 h (range: 8.5-278), familial history of hypertension: 21%, smoking: 24%, regular alcohol intake: 38%, coronary heart disease (ischemia and history of myocardial infarction): 17%, retinopathy (back-ground and proliferative): 24%. Results: sBP and dBP in the treated group are higher than in the group 2 (160.31 4- 19.36 vs. 153.5 4- 17.55 and 91.5 4- 14.8 vs. 87.25 -48.5 respectively, p < 0.1 for two comparisons). However the first group of patients are older (65.76 4- 9.37 vs. 58.4 4- 11.35 respectively, p < 0.02) and more obese (BMI: 30.55 4- 4.84 vs. 28.92 respectively, p < 0.1). The same group of patients shows markedly insulin resistance (12.37 4- 4.64 vs. 9.64 4- 4.15 respectively, p < 0.06), higher creatinine level (n.s) and microalbuminuria (134.58 4- 240 4- 98 vs. 27.93 4- 27.3 respectively, p < 0.08) than the second group of patients. Otherwise glycemic and lipidic parameters are not significantly different, but in group 1 are more patients with retinopathy (21% vs. 0% respectively, p < 0.04). In conclusion, treatment for hypertension in type 2 diabetes shows poor results on blood pressure due either to insulin resistance and/or patient compliance.
P385 Reduction of Blood Pressure and Albuminuria in Hypertensive Patients with Type 2 Diabetes Using Candesartan, Lisinopril and Their Combination CARL ERIK MOGENSEN, Mark E. Cooper. Medical Department. M, Aarhus University Hospital, Aarhus, Denmark; Department of Medicine, University Hospital Melbourne, Melbourne, Victoria, Australia Objectives: To study the effect of candesartan cilexetil (C) 16 mg o.d. and lisinopril (L) 20 mg o.d. and their combination (C+L) on blood pressure (BP) and urinary albumin excretion in hypertensive type 2 diabetic patients with microalbuminuria. Design and Methods: Patients (n= 199), aged 30-75 years with sitting diastolic blood pressure (DBP) 90-110 mmHg and urinary albumin/creatinine ratio (UACR) of 2.5-25 mg/mmol were, after 4 weeks of placebo treatment, randomised double blind to receive either, C or L monotherapy for 12 weeks followed by an additional 12 weeks of the same monotherapy or the combination of C+L. Results: After 12 weeks of monotherapy, both C and L reduced sitting BP (C 12.4/9.5 mmHg p<0.001; L 15.7/9.7 mmHg p<0.001) and UACR (C 30% p<0.001; L 46% p<0.001) with no significant difference between treatments. After the 24 week treatment period, UACR decreased in all treatment groups (C 24% p---0.052; L 39% p<0.001; C+L 50% p<0.001). At 24 weeks, the C +L treatment group had a BP reduction of 25.3/16.3 mmHg (p<0.001) as compared to baseline. This reduction was substantially and significantly greater than the reductions observed with monotherapy (C 14.1/10.4 p<0.001; L 16.7/10.7 p<0.001). Both drugs and their combination were well tolerated and there were no major differences in adverse event profiles. Importantly, no adverse effects were observed in the combination treatment group such as acute deterioration in renal function or symptomatic hypotension. Conclusion: ATt receptor blockade with candesartan and ACE inhibition with lisinopril both reduce BP and microalbuminuria (UACR) in hypertensive type 2 diabetic patients with microalbuminuria with no significant
Track 2. Clinical Research & Care difference between the treatments. The combination of candesartan and lisinopril reduced BP more than any of the monotherapies and appeared to be the most effective treatment in reducing UACR. Thus the combination of candesartan, and lisinopril, seems a highly effective and well tolerated treatment for reducing BP in hypertensive type 2 diabetic patients with microalbuminuria.
P386 12 Months Post UKPDS and HOT: Impact on BP Targets and Anfihypertensive Drug Prescribing in the Community M.N. MUNRO, R. Larenson, M.D. Feher. Beta Cell Diabetes Centre, Chelsea & Westminster Hospital, London, UK The influence of UKPDS and HOT trials results on community-based prescriptions of antihypertensive drugs in order to achieve lower BP targets for the observed clinical benefit has not been reported. From a single Primary Care Group in Southern England (population 42,000) patients with confirmed type 2 diabetes (n=415) were characterised by current BP recordings and number and class of antihypertensive drug used. From this group, BPs above that achieved in the trials (above 140/80mmHg) were observed in only 40% of subjects, while antihypertensive drug usage was recorded in 54%, of whom 33% were on two or more antihypertensive drugs. When medication usage was stratified according to BP control, 64% of subjects with a systolic BP> 140mmHg were receiving antihypertensive medication and 59% in those with a diastolic BP>80mmHg. Treatment with 2 or more antihypertensives was recorded in 34% in both the higher BP groups. (In comparison, two thirds of UKPDS and HOT patients were similarly treated). Only 3% of patients were on >3 antihypertensive agents. Low usage was recorded for beta-blockers (10%), alpha-blockers (4%) and A-II blockers (2%). Increased use was recorded for calcium channel blockers (18%), diuretics (20%) and ACEI (21%). These data show there has been implementation of evidence based practice in the community. "Newer" compared to "old" antihypertensive treatment appear to be widely used. The number of patients needing antihypertensive treatment will need to be almost doubled if trial-based BP targets are to be reached. In addition, the numbers taking 3 or more antihypertensive drugs will need to be increased nearly 10x if their management reflects UKPDS. The cost of implementing this in the short term is likely to be very substantial in Primary Care.
P387 New Drug Combinations in Diabetic Hypertension; Short Term Effects of Low Dose Moxonidine-ACEI Combination A. COX, A. Zambaninl, C. Mclntosfi, M.D. Feher. Beta Cell Diabetes Centre, Chelsea & Westminster Hospital, London, UK The recent major outcome trials In diabetic hypertension have highlighted the need for combination antihypertensive therapy in order to lower BP and reduce cardiovascular complications. There is little data on the role of moxonidine (a selective imidazoline receptor agonist) in combination antihypertensive treatment in patients with diabetes. In a cross-over study, eight subjects with type 2 diabetes and on conventional dose ACEI for hypertension (mean BP: 176/93, SD:26/6), were assessed three times: (1) after a 2 week run-in phase, with continuation of conventional dose ACEI (2) after 4 weeks low dose moxonidine (200mcg) combination with half usual dose ACEI treatment and (3) after 4 weeks treatment with only conventional dose ACEI. Standardised clinic BP measurements confirmed a mean reduction of 14/12mmHg (A dBP p<0.05 Wilcoxon) with low dose combination therapy and a 14/9mmHg increase (A sBP, dBP p<0.01) after moxonidine withdrawal and reintroduction of the usual dose ACEI. There were no significant changes in weight or fasting glucose or lipid profile. This study has shown the marked BP lowering effects of combining a low dose imldazoline agonist and ACEI, (as well as the effects of monotherapy
$87
withdrawal) and has the potential advantage of minimising drug related side-effects.
1'388 Idiotypic Antibodies in Autoimmunitary Diabetes Mellitus GUSTOVO ACOSTA 1, Maribel Hem~fndez2, Rocio Reyes 3, Martin Herrera4, Carlos Parrao 5, Rao Srinivasa6. J Immunology, Clinica de Inmunodiagntstico, M(xico, City, DE M(xico; 2 Immunology, Clinica de lnmunodiagn6stico, M(xico, City, DE M(xico; s Microbiology, Facultad de Medicina, UNAM, M~xico, City, DE M~xico; 4 Medicina lnterna, Hospital Jutrez de Mdxico, M(xico, City, DE Mdxico; 5 Laboratorio Clfnico, Hospital Judrez de Mtxico, Mdxico, City, DE M(xico; 6 Research and Development, Biomerica, CA, United States of America The regulation of the production of immunoglobulins by antibodies from the same person was postulated by Jerne when he demonstrated secuences of specific aminoacids in the antibodies of each person located in the variable portions of immunoglobulins which are genetically codified and can be antigenic and induce the production of new antibodies against these portions denominated idiotypes and regulate the production of autoantibodies to diminish the inflamatory effects in the pancreatic cells. In the current work the idiotypic induction to regulate the production of (IAA) in 6 patients with diabetes type 1, with a evolution time of 36 months that presents IAA peripheric blood quantified by ELISA and with a substitutive treatmen with human insulin. Individually the gamaglobulins of the 6 patients were purified by the Cohn method it consists of an initial precipitation with ethilic alcohol y then by cromatography affinity using human insulin fixed to Sepharosa 4B. Protocol of specific idiotypic antibodies induction: Daily administration of specific autologous autoantibodies via subcutaneous (0.5 ml) during 40 days. Protocol of inespecific idiotypic antibodies induction: autologous immunoglobulins were purified and administrated in a control group of 40 healthy persons with normal glucose levels and glycosilated hemoglobin at the begining of the study. At the end of the protocol circulanting antibodies weren't detected against human insulin (IAA) by the ELISA method in three patiens, diminishing significantly the dairy doses of insulin, and hemoglobin levels and glucose in fast remained in normal ranges at 60 days. In the control group there weren't variations in the concentration of glucose in fast and glycosilated hemoglobin during 40 days.
1'389 ~8-Cell Autoantibodies and Genetic Background Associated with Insulin Dependence in Adult-Onset Diabetes Mellitns SILVINA N. VALDEZ ~, Ana L. Villanueva l, Anabel Villalba 1, Ruben E Iacono 1, Mauricio P. Sica ', Alejandro C. Cardoso I, Maximiliano Wilda 2, C. Refi 3 Norberto Cedola 3, Gustavo Frechtel 2, Edgardo Poskus i. l Inmunologia, Facultad de Farmacia y Bioqu[mica, UBA e IDEHU (CONICET-UBA), Capital Federal, Buenos Aires, Argentina; 2 Gen(tica y Biolog[a Molecular, Facultad de Farmacia y Bioquimica, UBA, Capital Federal, Buenos Aires, Argentina; 3 Cenexa, Universidad Nacional de La PIata-CONICET, La Plata, Pcia de Buenos Aires, Argentina Immune-mediated Diabetes Mellitus (DM) is early detectable by determination of islet cell autoantibodies (markers). The most useful markers are the autoantibodies to insulin (IAA), antibodies to glutamic acid decarboxylase (GADA) and antibodies to protein tyrosine phosphatase (ICA512A). In this study we determined the presence of immunological and genetic markers in adult-onset diabetic patients. We studied 45 patients treated with insulin after two year from diagnosis ("fast-evolving insulin requiring